® Post-Approval Experience: Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval Carprovet (carprofen) adverse drug experience reporting. The categories of adverse reactions are listed in decreasing order of frequency by Flavored Tablets body system. Gastrointestinal: Vomiting, diarrhea, constipation, inappetence, melena, hematemesis, gastrointestinal ulceration, Non-steroidal anti-inammatory drug gastrointestinal bleeding, pancreatitis. For oral use in dogs only Hepatic: Inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic enzyme elevation, abnormal liver function test(s), hyperbilirubinemia, bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Labrador Retrievers. DESCRIPTION: Carprovet (carprofen) is a non-steroidal anti-inammatory drug (NSAID) of the propionic acid class that Neurologic: Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation. includes ibuprofen, naproxen, and ketoprofen. Carprofen is the nonproprietary designation for a substituted carbazole, Urinary: Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, 6-chloro-α-methyl-9H-carbazole-2-acetic acid. The empirical formula is C15H12ClNO2 and the molecular weight 273.72. tubular abnormalities including acute tubular necrosis, renal tubular acidosis, glucosuria. The chemical structure of carprofen is: Behavioral: Sedation, lethargy, hyperactivity, restlessness, aggressiveness. Hematologic: Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, blood loss anemia, epistaxis. Dermatologic: Pruritus, increased shedding, alopecia, pyotraumatic moist dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis. Immunologic or hypersensitivity: Facial swelling, hives, erythema. In rare situations, death has been associated with some of the adverse reactions listed above. Carprofen is a white, crystalline compound. It is freely soluble in ethanol, but practically insoluble in water at 25°C. To report a suspected adverse reaction call Dechra at (866) 933-2472. CLINICAL PHARMACOLOGY: Carprofen is a non-narcotic, non-steroidal anti-inammatory agent with characteristic For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or analgesic and antipyretic activity approximately equipotent to indomethacin in animal models.1 http://www.fda.gov/AnimalVeterinary/SafetyHealth. The mechanism of action of carprofen, like that of other NSAIDs, is believed to be associated with the inhibition of DOSAGE AND ADMINISTRATION: Always provide Client Information Sheet with prescription. Carefully consider the potential cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals.2 The constitutive cyclooxygenase, benets and risk of Carprovet and other treatment options before deciding to use Carprovet. Use the lowest effective dose COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, for the shortest duration consistent with individual response. The recommended dosage for oral administration to dogs is COX-2, generates prostaglandins involved in inammation. Inhibition of COX-1 is thought to be associated with 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inammatory activity. The specicity of a of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative particular NSAID for COX-2 versus COX-1 may vary from species to species.3 In an in vitro study using canine cell cultures, pain, administer approximately 2 hours before the procedure. Tablets are scored and dosage should be calculated in carprofen demonstrated selective inhibition of COX-2 versus COX-1.4 Clinical relevance of these data has not been shown. half-tablet increments. Carprofen has also been shown to inhibit the release of several prostaglandins in two inammatory cell systems: rat EFFECTIVENESS: Conrmation of the effectiveness of carprofen for the relief of pain and inammation associated with polymorphonuclear leukocytes (PMN) and human rheumatoid synovial cells, indicating inhibition of acute (PMN system) osteoarthritis, and for the control of postoperative pain associated with soft tissue and orthopedic surgeries was and chronic (synovial cell system) inammatory reactions.1 demonstrated in 5 placebo-controlled, masked studies examining the anti-inammatory and analgesic effectiveness of Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular immune responses.5-9 carprofen tablets in various breeds of dogs. Data also indicates that carprofen inhibits the production of osteoclast-activating factor (OAF), PGE1, and PGE2 by its Separate placebo-controlled, masked, multicenter eld studies conrmed the anti-inammatory and analgesic effectiveness inhibitory effects on prostaglandin biosynthesis.1 of carprofen tablets when dosed at 2 mg/lb once daily or when divided and administered at 1 mg/lb twice daily. In these Based upon comparison with data obtained from intravenous administration, carprofen is rapidly and nearly completely two eld studies, dogs diagnosed with osteoarthritis showed statistically signicant overall improvement based on absorbed (more than 90% bioavailable) when administered orally.10 Peak blood plasma concentrations are achieved in lameness evaluations by the veterinarian and owner observations when administered carprofen at labeled doses. 1-3 hours after oral administration of 1, 5, and 25 mg/kg to dogs. The mean terminal half-life of carprofen is approximately Separate placebo-controlled, masked, multicenter eld studies conrmed the effectiveness of carprofen tablets for the 8 hours (range 4.5-9.8 hours) after single oral doses varying from 1-35 mg/kg of body weight. After a 100 mg single control of postoperative pain when dosed at 2 mg/lb once daily in various breeds of dogs. In these studies, dogs presented intravenous bolus dose, the mean elimination half-life was approximately 11.7 hours in the dog. Carprovet is more than for ovariohysterectomy, cruciate repair and aural surgeries were administered carprofen preoperatively and for a maximum 99% bound to plasma protein and exhibits a very small volume of distribution. of 3 days (soft tissue) or 4 days (orthopedic) postoperatively. In general, dogs administered carprofen showed statistically Carprofen is eliminated in the dog primarily by biotransformation in the liver followed by rapid excretion of the resulting signicant improvement in pain scores compared to controls. metabolites (the ester glucuronide of carprofen and the ether glucuronides of 2 phenolic metabolites, 7-hydroxy carprofen ANIMAL SAFETY: Laboratory studies in unanesthetized dogs and clinical eld studies have demonstrated that carprofen is and 8-hydroxy carprofen) in the feces (70-80%) and urine (10-20%). Some enterohepatic circulation of the drug is observed. well tolerated in dogs after oral administration. INDICATIONS: Carprovet is indicated for the relief of pain and inammation associated with osteoarthritis and for the In target animal safety studies, carprofen was administered orally to healthy Beagle dogs at 1, 3, and 5 mg/lb twice daily control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs. (1, 3 and 5 times the recommended total daily dose) for 42 consecutive days with no signicant adverse reactions. Serum CONTRAINDICATIONS: Carprovet should not be used in dogs exhibiting previous hypersensitivity to carprofen. albumin for a single female dog receiving 5 mg/lb twice daily decreased to 2.1 g/dL after 2 weeks of treatment, returned to the pre-treatment value (2.6 g/dL) after 4 weeks of treatment, and was 2.3 g/dL at the nal 6-week evaluation. Over the WARNINGS: Keep out of reach of children. Not for human use. Consult a physician in cases of accidental ingestion by 6-week treatment period, black or bloody stools were observed in 1 dog (1 incident) treated with 1 mg/lb twice daily and in humans. For use in dogs only. Do not use in cats. 1 dog (2 incidents) treated with 3 mg/lb twice daily. Redness of the colonic mucosa was observed in 1 male that received All dogs should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate 3 mg/lb twice daily. laboratory tests to establish hematological and serum biochemical baseline data prior to, and periodically during, Two of 8 dogs receiving 10 mg/lb orally twice daily (10 times the recommended total daily dose) for 14 days exhibited administration of any NSAID should be considered. Owners should be advised to observe for signs of potential drug hypoalbuminemia. The mean albumin level in the dogs receiving this dose was lower (2.38 g/dL) than each of 2 placebo toxicity (see Information for Dog Owners, Adverse Reactions, Animal Safety and Post-Approval Experience). control groups (2.88 and 2.93 g/dL, respectively). Three incidents of black or bloody stool were observed in 1 dog. Five of PRECAUTIONS: As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic 8 dogs exhibited reddened areas of duodenal mucosa on gross pathologic examination.